patients with severe BPH and acute urinary retention UroToday Report: Science managed with indwelling catheters. to Clinical Practice Anatomy of Prostatic

A multi-disciplinary approach to Benign Knowing the vascular anatomy of the is good clinical Prostatic Hyperplasia (BPH) management: practice. BPH angiography and embolization will increase the Prostatic Arterial Embolization (PAE) knowledge of functional vascular anatomy and contribute to better clinical results with fewer complications. Primary and emerges as alternative therapy for men secondary prostatic arteries supply the prostate, arising from with severe benign prostatic hyperplasia the inferior vesical (vesico-prostatic artery), internal pudendal, and the . The most common Alberto A Antunes, Urology artery is the inferior vesical artery (vesico-prostatic artery). Francisco C Carnevale, Interventional Radiology The most common origin is the anterior trunk (represented University of São Paulo Medical School, Brazil on the third branch). Frequently seen is the pudendal artery origin. Usually one main pedicle is found on each side, but two main pedicles are possible (plus small accesory arteries).5 Keywords: Urology – Interventional Radiology—Benign Prostatic Hyperplasia- Prostatic Arterial Embolization— Urinary retention – Prostatic Artery--Embosphere® Differentiating BPH Symptoms microspheres A large portion of any primary care or urology practice Introduction consists of BPH management. The clinician should differentiate chronic prostatitis (CP) and chronic pelvic pain syndrome (CPPS) from BPH, and evaluate LUTS in terms of Benign prostatic hyperplasia (BPH) if left untreated can lead 8 storage versus voiding symptoms. Patients often present to acute urinary retention incontinence and urinary tract 8 with LUTS and then proceed to “watchful waiting.” As infections. Pathologically, 50 percent of men in their 50s will symptoms progress, oral medical therapy is often prescribed have BPH; 26-40 percent will have moderate to severe lower 1 followed by surgical intervention. IPSS or AUA symptom urinary tract symptoms (LUTS) between the ages 40-79. scores are used to assess progress. Ultimately therapeutic decisions are made between the patient and physician based As a first line of treatment, α-Blockers, 5α-reductase on symptoms and QoL, which may not relate to the degree of inhibitors, and combination therapy with the two have all bladder outlet obstruction or lose of other urologic functions. proved highly effective, in both trials and clinical practice.

Nevertheless, medical therapy does not work for everyone.6 Independent tissue specimen studies show 50 percent of men Kaplan et al. reported 30 percent of BPH patients fail with lower urinary tract symptoms (LUTS) and/or BPH will medication therapy within two years. Larger , as have inflammatory infiltrates, and patients with chronic determined by increased volume and elevated PSA, as well as inflammation have high symptom progression. Prostate higher baseline symptoms seem to predict failure.6 While volume has been shown to be a consistent marker for future transurethral resection of the prostate (TURP) is considered 1 disease development. Although, transurethral resection of the gold standard, some patients do not tolerate general the prostate (TURP) remains the gold standard for invasive anesthesia resulting in adverse events often related to the therapy, TURP is associated with erectile dysfunction in 10 urethral. percent of patients and ejaculatory disorders in 50-65 ______9 percent of patients. In TURP and laser TURP ejaculatory Complications from TURP 1,2 7 Retrograde ejaculation 50% disorders remain the primary side effect attributed to the Early urinary incontinence 30-40% damage to nerve bundles adjacent to the prostatic capsule. Erectile dysfunction 10% PAE may be an alternative treatment with fewer side effects. Reoperation in 5 years 5% Urethral stricture 2.2-9.8% 1, 4, 7 AUR by blood clots 2-5% BPH Related Symptoms Urinary infection 1.7-8.2%  Urinary frequency Impotence < 5%  Urgency and nocturia Blood transfusion 0.4-7% Voiding irritation and discomfort for 2-4 weeks_  Hesitancy (difficulty initiating urinary stream)

In response to these challenges, the São Paulo multi-  Decreased or intermittent force of urinary disciplinary team representing urologists and interventional stream radiologists developed an alternative, minimally-invasive,  Straining (Valsalva maneuver) therapeutic treatment using arterial embolization and local  Dribbling (loss of small amounts of urine) anesthetic. The São Paulo pilot study involved eleven male  Feeling of incomplete bladder emptying  Abdominal pain Management of Advanced BPH approach. Embosphere® Microspheres 300-500 µm (Merit Medical) was the embolic used in the procedure. Oral medications (alpha-blockers and 5-alpha reductase Microcatheters Embocath Plus (Merit Medical) and Progreat inhibitors) are widely accepted as front-line therapy for (Terumo) were specified to navigate the prostate arteries. symptomatic BPH and LUTS. An AUA Gallop Poll reported 88 percent of urologists recommend alpha-blockers for men The PAE technique involved a superselective (bilateral) with moderate urinary symptoms and evidence of prostate angiographic study of the superior vesical artery, obturatory enlargement of less than 40cc. artery, inferior vesical artery, middle rectal artery, and internal pudenda artery. If these arteries fed the prostate. In The therapeutic goal of Prostatic Arterial the pilot study, each patient was injected with 300-500 micron Embosphere® microspheres until the endpoint of Embolization (PAE) is to enable long term relief of stasis was achieved bilaterally, if posible. symptoms in an economical and efficient manner without the need for recurrent procedures. Standard transrectal ultrasound and magnetic resonance imaging were used to evaluate the gland before and after the The PAE technique models the uterine fibroid embolization PAE. Images bellow are MRI before (left) and 30-day post procedure commonly done by interventional radiologists. embolization (right) showing reduction of the prostate size Carnevale developed an outpatient PAE procedure using local with avascular areas: anesthetic. This procedure recognizes the five different arterial branches of the prostate anatomy as evaluated through angiography and contrast. The arteries are often represented by tortuous corkscrew vasculature and best navigated with a microcathether.

Pre-PAE 75 gm @30days post-PAE 46 gms Prostatic Arterial Embolization Clinical (38.7 % prostate reduction) Investigation Protocol The PAE protocol, although designed as an outpatient Prostate embolization for prostatic hemorrhage was first procedure, did admit these patients overnight for observation published 35 years ago by Mitchell et al. J Urol 1976 and since all of the patients lived a great distance from the more recently by Rastinehad et al. Urology 2008. Sun et al medical center. All patients experienced mild to moderate reported a PAE animal (pig) study comparing Embosphere® post surgery side effects. microspheres to a control group and demonstrated a 10 (Results based on Carnevale et al CVIR 2010; abstracts/presentations: CIRSE significant prostate reduction. 2010, RSNA 2010, GEST 2011 and AUA 2011)

FC Carnevale participated in animal studies in 2007 and Prostastic Arterial Embolization Technical Goals results were presented during the Annual Meeting of the Society of Interventional Radiology (SIR 2008). After that a multi-disciplinary PAE procedure for a phase 1 pilot study that began June 2008 and ended November 2010 was performed at the University of Sao Paulo Medical School. Both the interventional radiologist and the urologist were involved in patient selection and follow-up. Inclusion criteria included patients with prostates 30 to 90 gm and acute urinary retention (AUR) refractory to alpha-blockers. Eleven patients Interior Vesical Artery Left Prostatic Lobe Opacification with AUR due to BPH and managed with indwelling catheters were identified. The urologist did a full urologic work-up prior to the study; prostate malignancy was ruled out. The work-up included: a patient evaluation, digital rectal examination, urodynamic testing, prostate specific antigen, transrectal ultrasound, magnetic resonance imaging, prostate biopsy (if concern and according to PSA), IPSS (International Prostate Symptom Score), and a IIEF (International Index of Erectile Function) rating. Prostatic Branches Stasis achieved The prostate size in this patient sample ranged from 30 to 90 gms and the mean patient age was 68.5 y/o (range, 59 to 78 y/o). An angiosuite was used for the procedure. Local anesthesia was given using the right transfemoral arterial Results: References

All patients had indwelling catheters and following the PAE 1. AUA Practice Guidelines, BPH Committee, 2010 procedure, ten of the 11 patients demonstrated an average 2. Burnett AL. J Urol 2006; 175:S19-S24 3. Carnevale FC, Antunes AA et al CVIR 2010; 33(2):355-361 30 percent reduction in the prostate volume. Symptom relief 4. Emberton M et al. Urology 2003; 61:267–73 and catheter removal was achieved in 10 patients with a 5. Garcia-Monaco R, Prostatic Anatomy, GEST 2011: presentation mean time of 12 days. After a three year follow-up in two 6. Kaplan S, Rev. Urol 2005(Suppl 7):S34-S39 patients and a minimum of five months follow-up in all 7. Rassweiler J et al. Eur Urol. 2006; 50:969-79 patients; 91 percent clinical success was achieved based on 8. Stroup S. , AUA 2011: Abstract 1721 12 PAE procedures. Overall, QoL factors significantly 9. Mauro MA, Radiology 2008; 246:3. 657-658. improved for ten f the 11 patients. Of the 11, one patient had 10. Sun F, Radiology 2008; 246(3):783-789 ______a mean prostate reduction of 5%, and after two bilateral embolizations was referred for TURP. The surgeon indicated This educational supplement is made possible this patient experienced a much smaller blood loss compared to other TURP patients. through an educational grant from Merit Medical Systems, Inc. www.merit.com

Technical success: 75% (3) Unilateral PAE; (9) Bilateral PAE Clinical success: 91% (11 of 12 PAE procedures)

Prostate Volume Reduction

1 3 6 9 18 month months months months months 10 pts 10 pts 9 pts 3 pts 2 pts USG 27.3% 34.3% 36.0% 25.9% 29.6% MRI 25.7% 29.7% 32.4% 24.6% 32.9%

Clinical Follow-up: 5 months to 3 years

IPSS score: Mild side effects at 1 month (7.1), thereafter ranged from 2.2-4.0. Erectile dysfunction IEEF index: at 1 month (15.5) mild- moderate; thereafter improved to mild to no dysfunction within 3 years. QUOL: The qualify of life after PAE ranged from delighted to pleased.

Conclusion

BPH can be safely treated by PAE with low side effects rates and can reduce prostate volume by more than 30 percent. In addition to acute urinary retention, PAE may be appropriate for patients with history of TURP or pelvic trauma with alterations in pelvic anatomy, for different prostate sizes, for poor surgery candidates or ASA class group V, and before other treatments to reduce the risk of bleeding or improve overall results. Larger studies with more data supporting PAE are necessary to validate our observations. Overall, a multidisciplinary approach between the primary physician or urologist and interventional radiologist provides optimum continuity of care.